Is DPP8 p.Ile225Val (c.673A>G) pathogenic?

DPP8 p.Ile225Val (c.673A>G) is classified Uncertain significance in DPP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-17). AlphaMissense: likely benign (0.0687); Very rare (popmax 0.00171%, nfe).

How common is DPP8 p.Ile225Val (c.673A>G) in the general population?

DPP8 p.Ile225Val (c.673A>G) is very rare (popmax 0.00171%, nfe) (gnomAD).

What do computational predictors say about DPP8 p.Ile225Val (c.673A>G)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

DPP8 p.Ile225Val

c.673A>G · VCV3504983

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00171%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 49 kb · p 0.00056 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I241V vs ClinVar I225V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00171% European (non-Finnish) · 20/1,166,352 alleles

Filtering AF 0.00112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00091%

Overall 0.00138% 22/1,592,148 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00171%	58,318
African / African-American	0.00134%	74,620
South Asian	0.00115%	86,748

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DPP8
Protein: p.Ile225Val
Coding: c.673A>G
MANE Select: NM_130434
Type: single nucleotide variant
Location: chr15:65497906 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 19 PDB

Full DPP8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP8 p.Ile225Thr Uncertain significance ★ ⚠ same residue
DPP8 p.Thr182Met Uncertain significance ★★ ⚠ same type
DPP8 p.Thr227Ser Uncertain significance ★★ ⚠ same type
DPP8 c.1017+1G>T Uncertain significance ★ same type
DPP8 c.259+1G>C Uncertain significance ★ same type
DPP8 c.-12+1811G>T Uncertain significance ★ ⚠ same type
DPP8 c.-12+1828C>T Uncertain significance ★ ⚠ same type
DPP8 p.Ala110Thr Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dpp8-p-ile225val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown